Zhou Lu-Lu, He Xing-Ying, Xu Feng-Ying, Du Bo-Xiang, Zou Zui, Shi Xue-Yin
Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
Exp Lung Res. 2014 Nov;40(9):467-73. doi: 10.3109/01902148.2014.948231.
Pulmonary fibrosis (PF) is an insidiously progressive scarring disorder of the alveoli and is associated with high mortality. Currently, therapies available are associated with restricted efficacy and side effects. This study aimed to investigate the effect of chitosan aerosol inhalation on lipopolysaccharide (LPS)-induced pulmonary remodeling and fibrosis in rats.
A rat model of PF was established by intratracheal injection of LPS (5 mg/kg). Chitosan was nebulized to rats from day 4 to 28 after LPS injection. We analyzed the effect of chitosan on LPS-induced pulmonary remodeling and fibrosis by hematoxylin-eosin staining (HE), Masson staining, and the determination of the hydroxyproline content. The expression intensities of matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were analyzed by western blots.
Histological assessments showed that chitosan aerosol inhalation attenuated the fibrotic changes in LPS-induced PF in rats. Compared with the LPS group, the fibrosis parameters were significantly improved in the LPS + chitosan group (LCh group), although not as good as those of the control group. The expressions of MMP-3 and TIMP-1 in the LCh group were markedly less than that of the LPS group on the 28th day.
Our findings show that chitosan aerosol inhalation inhibits the expression of MMP-3 and TIMP-1, and ameliorates LPS-induced pulmonary remodeling and fibrosis in rats.
肺纤维化（PF）是一种肺泡的隐匿性进行性瘢痕形成疾病，且与高死亡率相关。目前，可用的治疗方法疗效有限且伴有副作用。本研究旨在探讨壳聚糖气雾剂吸入对脂多糖（LPS）诱导的大鼠肺重塑和纤维化的影响。
通过气管内注射LPS（5 mg/kg）建立PF大鼠模型。在LPS注射后第4天至第28天对大鼠进行壳聚糖雾化。我们通过苏木精-伊红染色（HE）、Masson染色以及羟脯氨酸含量测定来分析壳聚糖对LPS诱导的肺重塑和纤维化的影响。通过蛋白质印迹法分析基质金属蛋白酶-3（MMP-3）和金属蛋白酶组织抑制剂-1（TIMP-1）的表达强度。
组织学评估显示，壳聚糖气雾剂吸入减轻了LPS诱导的大鼠PF的纤维化改变。与LPS组相比，LPS +壳聚糖组（LCh组）的纤维化参数显著改善，尽管不如对照组。在第28天，LCh组中MMP-3和TIMP-1的表达明显低于LPS组。
我们的研究结果表明，壳聚糖气雾剂吸入可抑制MMP-3和TIMP-1的表达，并改善LPS诱导的大鼠肺重塑和纤维化。
